Department of Neurosurgery, Xuanwu Hospital Capital Medical University, Beijing, 100053, China.
Cell Therapy Center, Beijing Institute of Geriatrics, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases, and Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, 100053, China.
Mol Biol Rep. 2024 Nov 7;51(1):1126. doi: 10.1007/s11033-024-10073-y.
Adamantinomatous craniopharyngiomas (ACPs), commonly seen in pediatrics and adults often present with large cystic cavities that can compress surrounding tissues, causing severe visual and endocrine symptoms. Complete resection of cystic ACP is challenging, frequently leading to postoperative recurrence. The composition of the cystic fluid is complex, and to date, there has been limited research focusing on exosomes within ACP cyst fluid.
We collected cyst fluid from 12 ACP patients and confirmed the presence of exosomes. Subsequently, we conducted exosomal proteomic analysis using LC-MS/MS. The patients were divided into pediatric and adult groups for the analysis of differential protein enrichment, followed by comprehensive bioinformatics analysis, including GO analysis, KEGG analysis, and PPI network analysis, among other functional pathway and protein interaction analyses. Immunohistochemistry was used to determine the tissue expression distribution of the differential protein APOA1.
In our data analysis, 64 significantly differentially expressed proteins were identified, with 37 being overexpressed in the pediatric group and 27 in the adult group. Our results revealed that exosomal proteins in the pediatric group were predominantly enriched in modules and pathways related to high-density lipoprotein particle, apolipoprotein receptor binding, and the PPAR signaling pathway. Additionally, APOA1, as the hub protein with the highest connectivity in the differential protein interaction network, may play a critical role in β-amyloid metabolism pathways in pediatric ACP.
This study is the first to construct a proteomic map of ACP cyst fluid exosomes, suggesting significant differences in the tumor microenvironment's lipid metabolism between pediatrics and adults.
造釉细胞瘤（adamantinomatous craniopharyngiomas，ACPs）常见于儿科和成人，常表现为大的囊性腔，可压迫周围组织，导致严重的视觉和内分泌症状。囊性 ACP 的完全切除具有挑战性，常导致术后复发。囊液的成分复杂，迄今为止，针对 ACP 囊液中的外泌体的研究有限。
我们收集了 12 例 ACP 患者的囊液并证实存在外泌体。随后，我们使用 LC-MS/MS 进行了外泌体蛋白质组学分析。我们将患者分为儿科和成人组，分析差异蛋白的富集情况，然后进行全面的生物信息学分析，包括 GO 分析、KEGG 分析和 PPI 网络分析等功能途径和蛋白质相互作用分析。免疫组织化学用于确定差异蛋白 APOA1 的组织表达分布。
在数据分析中，我们鉴定出 64 个显著差异表达的蛋白，其中 37 个在儿科组中过表达，27 个在成人组中过表达。我们的结果表明，儿科组外泌体蛋白主要富集在与高密度脂蛋白颗粒、载脂蛋白受体结合和 PPAR 信号通路相关的模块和途径中。此外，APOA1 作为差异蛋白相互作用网络中连接度最高的枢纽蛋白，可能在儿科 ACP 的β-淀粉样蛋白代谢途径中发挥关键作用。
本研究首次构建了 ACP 囊液外泌体的蛋白质组图谱，提示儿童和成人肿瘤微环境的脂质代谢存在显著差异。
